Neurotoxicity of anesthetics in the developing neurons: in vitro model to assess the neurotoxicity in human induced pluripotent stem cell derived neurons.

2014 Fiscal Year Final Research Report

• Project/Area Number: 25670666
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Anesthesiology
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: MAKITA Koshi 東京医科歯科大学, 医歯(薬)学総合研究科, 教授 (20199657)
• Co-Investigator(Renkei-kenkyūsha): ITO Hiroyuki 東京医科歯科大学, 医学部附属病院, 助教 (80595554) ; UCHIDA Tokujiro 東京医科歯科大学, 大学院医歯学総合研究科, 准教授 (40262183)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Keywords: iPS細胞由来神経細胞 / 麻酔薬 / 毒性評価 / ケタミン / ミトコンドリア

Outline of Final Research Achievements

To study the toxic effect of anesthetic drugs on human neurons, an experimental model using cultured neurons derived from human induced pluripotent stem cells (iPSCs) was examined, and the mechanisms of their toxicity were studied. We studied ketamine toxicity in this study, and we established an in vitro model to assess the neurotoxicity in iPSC-derived neurons. The present data indicate that initial mitochondrial dysfunction and autophagy may be resulted from inhibitory effect of ketamine on the mitochondrial electron transport system. Higher ketamine concentration can induce ROS generation and apoptosis in human neurons, and these mechanisms underlie ketamine-induced neural toxicity.

Free Research Field

麻酔学